Identification of the targets of autoreactive T cells is important for understanding the pathogenesis of many autoimmune diseases. In multiple sclerosis, myelin proteins are thought to be the targets of autoreactive T-cell responses. In the present study, the ability of self peptides derived from human myelin proteins to induce autoreactive CD8+ T-cell responses were assessed. Peptide sequences from human myelin basic protein (MBP), proteolipid protein (PLP), myelin-associated glycoprotein (MAG), and myelin oligodendrocyte glycoprotein have been identified that bind to and form stable complexes with HLA-A2. MBP 110-118, PLP 80-88, MAG 287-295, MAG 509-517, and MAG 556-564 were all able to induce peptide-specific HLA-A2-restricted CD8+ cytotoxic T-lymphocyte (CTL) responses in vitro in HLA-A2+ individuals. CTLs specific for MBP 110-118 and MAG 556-564 produced tumor necrosis factor alpha and a subset of these clones also produced interferon gamma. These results demonstrate that (i) self peptides derived from human myelin proteins can induce autoreactive CD8+ CTLs and (ii) these CD8+ T cells produce cytokines thought to be important in mediating demyelinating disease. These studies provide an experimental approach for the assessment of CD8+ T- cell responses in such autoimmune diseases. Most peptides that bind to a particular major histocompatibility complex class I molecule share amino acid residues important for binding at one or two positions. Sequence analyses of peptides bound to HLA-B14 revealed at least four candidates for these so-called anchor residues: Arg at P2, Tyr at P3, Arg at P5, and Leu at P9. Combinations of any three of these amino acids sufficed for binding to HLA-B14 in vitro. Using this information, we identified an antigenic peptide critical for cytotoxic T lymphocyte recognition of influenza virus-infected cells. Molecular models of HLA-B14 peptide complexes were constructed to investigate how the potential anchor residues might function. An ovalbumin (OVA)-specific T cell line (TCL) was established from a patient with hen egg allergy. The TCL was CD4+, expressed an alpha beta T cell receptor, and recognized OVA presented by HLA-DR10. Based on the response of the TCL to synthetic OVA peptides, it was found that the TCL recognized OVA 323-339. The TCL secreted high levels of IL-5, but undetectable amounts of IL-2, interferon-gamma, and IL-4 when stimulated with OVA or the OVA 323-339 peptide. Since IL-5 is an important growth and chemotactic factor for eosinophils, it is possible that these OVA 323-339 specific T cells can contribute to human egg allergy. To our knowledge, this is the first demonstration of food allergen-specific TCL and identification of a T cell epitope possibly related to the allergic reaction to food antigens. An analog peptide of the OVA 323-339, which is known to strongly bind to I-Ad, partially inhibited the response of the TCL to OVA 323-339 presented by HLA-DR10, raising the possibility of peptide-based immunotherapy of food allergy.